Zika Virus Infects Human Cortical Neural Precursors and Attenuates Their Growth
By Hengli Tang, Christy Hammack, Sarah C. Ogden, Z. Wen, Xuyu Qian, Yujing Li, Bing Yao, Jaehoon Shin, Feiran Zhang, Emily M. Lee and 5 more. Cell Stem Cell, 2016
1,217 citations recorded by the source corpus.
SUMMARY The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV MR766, serially passaged in monkey and mosquito cells, efficiently infects human cortical neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell cycle-related pathways. Our results identify human cortical neural precursor cells as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.
Subfields: Epidemiology, Infectious Diseases, Public Health, Environmental and Occupational Health
View Paper: https://www.semanticscholar.org/paper/b65ce11a4e99d202b1a1e7272b7e3ea5da3c570b
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Citations in the corpus
- Brain Region-specific Organoids using Mini-bioreactors for Modeling ZIKV Exposure (2016, neutral): “Modeling ZIKV Exposure ZIKV was prepared and titered as previously described (Tang et al., 2016).”
- Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection (2016, neutral): “adults (6) and congenital birth defects including microcephaly in the developing fetus (5, 7, 8), likely through its ability to infect human neural progenitor cells (9).”
- Zika virus: History, emergence, biology, and prospects for control. (2016, background): “Another study determined that ZIKV can infect human neural progenitors derived in vitro by inducing pluripotent stem cells (hiPSCs), which suggests the virus could have the capacity to infect neuroblasts in vivo (Tang et al., 2016).”
- A Mouse Model of Zika Virus Pathogenesis (2016, background): “…high levels of ZIKV viral RNA were observed in CNS tissues of Ifnar1−/− mice (>106 FFU equivalents per gram in the brain and spinal cord), confirming the neurotropic potential of the virus (Bell et al., 1971; Martines et al., 2016; Mlakar et al., 2016; Sarno et al., 2016; Tang et al., 2016).”
- Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice. (2016, background): “In addition, ZIKV strain MR766 has been shown to be capable of infecting NPCs derived from human induced pluripotent stem cells (hiPSCs) (Tang et al., 2016).”
- Zika Virus Depletes Neural Progenitors in Human Cerebral Organoids through Activation of the Innate Immune Receptor TLR3 (2016, positive): “Furthermore, recent studies show that ZIKV can infect human iPSC-derivedneural progenitor cells (NPCs) in vitro, resulting in dysregulation of cell-cycle-related pathways and increased cell death (Tang et al., 2016).”
- Zika virus in the Americas: Early epidemiological and genetic findings (2016, neutral): “The detection of ZIKV in fetal brain tissue (17, 20) and amniotic fluid (21) supports the hypothesis that the virus is transmitted from mother-to-child (22) and the virus infects neural progenitor cells in vitro (23).”